Virus infections may cause a great number of diseases that creates a serious threat to health and survival of mankind. For the last 20 years no less than 30 entirely new infectious agents have been discovered such as: HIV, viral hepatitises, acute and long-lasting diarrhoea, hemorrhagic fever (Ebola, Venezuelan, Brazilian, Rift valleys) [a) Lednicky J. A., Rayner J. O. Uncommon respiratory pathogens. Curr. Opin. Pulm. Med. 2006, 12(3), 235-239. b) Hayden F. G. Respiratory viral threats. Curr. Opin. Infect. Dis. 2006, 19(2), 169-178]. In particular, special anxiety is caused by the possibility to get sick with named avian influenza [a) Liu J. P. Avian influenza-a pandemic waiting to happen? J. Microbiol. Immunol. Infect. 2006, 39(1), 4-10. b) Henter J. I.; Chow C. B.; Leung C. W, Lau Y. L. Cytotoxic therapy for severe avian influenza A (H5N1) infection. Lancet. 2006 367(9513), 870-873. Review]. According to statistical data 60-65% of epidemic infections have viral ethiology. Because of interaction complexity in triad “virus—host's organism—drug”, most of modern antiviral drugs in the course of therapy exhibit side effects and form resistant virus strains [Jain R., Clark N. M., Diaz-Linares M., Grim S. A. Limitations of current antiretroviral agents and opportunities for development. Curr. Pharm. Des. 2006, 12(9), 1065-1074.]. At present, the number of antiviral drugs that could be used in clinical practice is extremely limited—only 43 substances of low molecular weight [http://integrity.prous.com/integrity], that is far from satisfying requirements of prophylaxis and treatment of virus diseases. Besides, there are a lot of virus infections causing diseases for treatment of which there are no chemotherapeutic agents. It is referred, for example, to the diseases caused by viruses of papilloma, adenoviruses, herpes-6, variola, syndrome SARS, hemorrhagic fevers, fever of the Western Nile, avian influenza and so on [De Clercq E. Recent highlights in the development of new antiviral drugs. Curr Opin Microbiol. 2005, 8(5), 552-560].
Therefore the development of new antiviral drugs, in particular, with new mechanism of antiviral action, high activity, and low toxicity is of great importance now.
Anti-influenza drug Arbidol based on the pharmaceutical composition comprising ethyl 6-bromo-4-[(dimethylamino)methyl]-5-hydroxy-1-methyl-2-(phenylthiomethyl)-1H-indole-3-carboxylate hydrochloride as an active ingredient is well known [Arbidol, PCT Int. Appl. WO 9008135, 1990],

Arbidol is used for prophylaxis and treatment of diseases caused by influenza viruses. It demonstrates the ability to induce interferon and shows immunomodulating effect. [Arbidol. Drugs R. D. 1999, September; 2(3), 171-172. Gluskova, T.; Glushkov, R. Arbidol is Interferon inductor, immunomodulator, antioxidant. Rev. Esp. Quimioter. 2000, 13(Suppl. 2), Abstr. M182].
However, the main disadvantage of Arbidol is its high cellular toxicity (CC50=10-20 mM) and, as a result of it, small therapeutic window or low selectivity index (SI50). For influenza virus, for example, it is equal only to 2.69 (on cellular line MDCK TC50=62.5 μg/ml and IC50=23.2 mkg/ml) [PCT Int Appl. WO 2005/087729 A1, 2005]. Its toxicity is even higher on some other cellular lines (CC50=15-25 μg/ml) [Brooks M J: Studies with the antiviral drug arbidol [PhD thesis]. Melbourne, Australia: RMIT University; 2003].
There are known antiviral pharmaceutical compositions comprising as active ingredients Arbidol analogs of the general formula A. [PCT Int Appl. WO 2004060873, 2004; PCT Int Appl. WO 2005087729 A1, 2005. Bioorg. Med. Chem. 2006, 14(4), 911-917],
wherein: R1 represents alkyl or cycloalkyl; R2 and R3 independently of each other represent amino group substituent selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, or R2 and R3 together with the nitrogen atom they are attached to form through R2 and R3 optionally substituted azaheterocyclyl; W represents substituted mercapto group.
Arbidol analoges of the general formula A exhibit also suppressing activity towards influenza A and B viruses, as well as viruses of hepatitis B (HBV) and human immunodeficiency virus (HIV) [Bioorg. Med. Chem. 2006, 14(4), 911-917. PCT Int Appl. WO 2005/087729 A1, 2005]. However, Arbidol analoges of the general formula A, as well as Arbidol itself, show high cellular toxicity and, as a result of it, low selectivity index. Thus, for example, selectivity index for this series of compounds towards hepatitis B is, as a rule, <10 (SI50=1.81-10.8) [Bioorg. Med. Chem. 2006, 14(4), 911-917].
There are also known more effective Arbidol analoges representing substituted 5-hydroxy-1-methyl-2-((dimethylamino)methyl)-1H-indole-3-carboxylates of the general formulas B1 and B2 [PCT Int Appl. WO 2007/136300 A2, 29 Nov. 2007; PCT Int Appl. WO 2007/136302 A2, 29 Nov. 2007],
wherein: R represents a cyclic system substituent selected from hydrogen, halogen, cyano group, optionally substituted aryl or optionally substituted heterocyclyl; R2 represents a lower alkyl; R3 represents an amino group substituent selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl.
There are known various substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids and esters thereof, exhibiting various types of biological activity: antiinflammatory, antiarthritis, anxiolytic, analgestic and so on. In particular, there are known 2-(2-methyl-5-methoxy-1H-indol-3-yl)acetic acid A1(1) [U.S. Pat. No. 3,161,654, DE 1232150], its ester A1(2) [Arzneim. Forsch. 37 (7), 806-813, 1987] and substituted 2-(1-benzoyl-2-methyl-5-methoxy-1H-indol-3-yl)acetic acids and esters thereof of the general formula A2 [BE 0858897, DE 3235850, EP 0078765, EP 0237495, CS 194283, CS 194284, FR 1540724, U.S. Pat. No. 4,136,194, U.S. Pat. No. 4,181,740, U.S. Pat. No. 5,436,265, U.S. Pat. No. 4,455,316, JP 1999043467, EP 1510205, JP 2004175723, JP 2005047906, JP 2005047907, JP 2005145931, JP 2005145932, JP 2005213192, JP 2006045099, JP 2006151836, JP 2006241341, JP 2006248922, JP 2007007189, US 2006178347, U.S. Pat. No. 6,051,587, WO 1987002891, WO 1990000545, WO 1998009948, WO 2000004897, WO 2000004897, WO 2000044705, WO 2001062085, WO 2001095913, WO 2002065977, WO 2003097057, WO 2004094409, WO 2004010994, WO 2005002525, WO 2005007650, WO 2005013980, WO 2005039565, WO 2005074992, WO 2005079856, WO 2005094788, WO 2005099674, WO 2006020994, WO 2006051818, WO 2006051819, WO 2006070672, WO 2006070673, WO 2006096955, WO 2006126214, WO 2007000842, WO 2007014476, WO 2007018210, WO 2007046318, WO 2007005941, WO 2007127725, WO 2007014476],
wherein: R3 represents hydrogen, optionally substituted C1-C5-alkyl, optionally substituted aryl; R1a represents 4-F, 4-Cl, 4-CF3, 4-CF3O, 4-N3, 2,4,6-Cl3.
There are also known substituted 2-(1-acyl-2-methyl-5-methoxy-6-fluoro-1H-indol-3-yl)acetic acids A3(1)-A3(7) [WO 2006036994, WO 2005002525], substituted 2-(1-benzyl-2-methyl-5-methoxy-6-chloro-1H-indol-3-yl)acetic acids A4(1), A4(2) [WO 2005002525, WO 2007022501], substituted 2-(1-benzoyl-2-methyl-5-methoxy-6-chloro-1H-indol-3-yl)acetic acids A5(1), A5(2), [WO 2005002525], 2-[1-(3-phenylacryloyl)-2-methyl-5-methoxy-1H-indol-3-yl]acetates A6(1), A6(2), A6(3) [WO 1994006769], 2-(1-benzoyl-5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids A7(1), A7(2), A7(3), A7(4) [WO 2005037227, WO 2005002525, WO 2006036994], [2-(1-methylpiperidin-4-yl)-5-hydroxy-2-methyl-1H-indol-3-yl]acetic acid A8(1), its ethyl ester A8(2) and 2-(1-heterocyclyl-2-methyl-5-methoxy-1H-indol-3-yl)acetic acids A9(1), A9(2), A9(3) [WO 2003066047] and pharmaceutically acceptable salts thereof A10(1)-A10(4) [DE 3036367, WO 1997003678, WO 2006099677, WO 2006099684, WO 2006099685],

However, substituted 2-(5-hydroxy-2-methyl-1H-indol-3-yl)acetic acids and esters thereof exhibiting antiviral activity, including compounds A1-A10, have not been known up to now.
Searching for highly effective antiviral drugs is one of the main directions for the development of new pharmacological remedies for treatment of wide range of virus infections now. In this context design of new antiviral active ingredients, pharmaceutical compositions and medicaments, methods for their preparation and application are of vital importance.